The work we have performed over the past 8 years has shown that almost all of the recipients of renal allografts who develop antibody to vascular endothelial cells experience irreversible graft rejection. Since vascular endothelial cells have been documented to be a primary target in the pathogenesis of rejection, the determination of preformed antibody to donor vascular endothelial cells is important in order to explain the almost uniform graft rejection seen in these patients. We have shown the vascular endothelial cell antigen system is also expressed on the peripheral blood monocyte and have standardized a crossmatch technique to be used pretransplant. This work has led us to the conclusion that patients with a positive monocyte crossmatch with their living-related donor should not be transplanted with that donor. Over the past few years, we have been providing this service to other transplant centers upon request and the response has increased. Sera screening protocols have enabled us to begin to assign tentative specificities through collection of serum from patients exhibiting antibody specific to vascular endothelial cells and we have made this sera available to other labs doing similar work. Work is continuing to define the cell specificity of the antigen system since there is some controversy as to whether or not the VEC/monocyte antigen system is expressed on granulocytes. We wish to continue this work so we may (a) continue screening for the presence of preformed antibody to donor vascular endothelial cells and provide this service to other transplant centers, (b) continue sera screening protocols so that we may continue to identify potential specificities and make the sera available to other researchers and future international workshops on vascular endothelial cell/monocyte antigens, (c) continue to develop reagents to facilitate the prospective tissue typing and matching for the antigens within this system and (d) evaluate the cellular mediated response to this antigen system using three established assays for cellular mediated immunity.